Gamma-hydroxybutyric acid endogenous production and post-mortem behaviour – The importance of different biological matrices, cut-off reference values, sample collection and storage conditions

• Review of several crucial aspects related to GHB forensic toxicology evaluation.
• Cut-off reference values evaluation for different biological samples.
• Description of specific sampling care and samples' storage conditions.
• GHB values interpretation in different biological samples.
• Reference to drug interactions and GHB's known metabolites.

Gamma-Hydroxybutyric Acid (GHB) is an endogenous compound with a story of clinical use, since the 1960's. However, due to its secondary effects, it has become a controlled substance, entering the illicit market for recreational and “dance club scene” use, muscle enhancement purposes and drug-facilitated sexual assaults. Its endogenous context can bring some difficulties when interpreting, in a forensic context, the analytical values achieved in biological samples. This manuscript reviewed several crucial aspects related to GHB forensic toxicology evaluation, such as its post-mortem behaviour in biological samples; endogenous production values, whether in in vivo and in post-mortem samples; sampling and storage conditions (including stability tests); and cut-off reference values evaluation for different biological samples, such as whole blood, plasma, serum, urine, saliva, bile, vitreous humour and hair. This revision highlights the need of specific sampling care, storage conditions, and cut-off reference values interpretation in different biological samples, essential for proper practical application in forensic toxicology.